The goal of this research is to define the relative roles of intra- and extramitochondrial genetic systems in determining cellular and mitochondrial phenotype. Our object is to determine molecular principles by which the information in mitochondrial DNA influences the processes of differentiation. We propose to apply both genetic and biochemical techniques to this end. Mitochondria bearing altered DNA will be introduced into a group of yeast mutants bearing mutant nuclear genes which modify aspects of mitochondrial biogenesis, and the resulting interactions will be analyzed by appropriate measurements of spectra, respiration and growth. The molecular bases of the developmental abnormalities associated with these mutant genes and related functional aberrations will be investigated through an analysis of biochemical activities of isolated mitochondria and a study of the properties of mitochondrial proteins and mitochondrial nucleic acids.